AB0392 EFFICACY AND SAFETY OF UPADACITINIB IN A CHINESE SUBGROUP OF PATIENTS WITH RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS
Authors: X. Zeng, Y. Liu, J. Hu, J. Li, Y. Wang, D. Zhao, L. Wu, Z. Xiao, Z. Li, J. Xu, S. Meerwein, Y. Xie, P. Liang
Journal: Annals of the Rheumatic Diseases (2022)

Background Upadacitinib (UPA) was effective in global Phase 3 trials in rheumatoid arthritis (RA) patients (pts) with inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Objectives To assess the efficacy and safety of UPA in csDMARD-IR pts with RA in Chinese subgroup from a Phase 3, randomized, double-blind, placebo (PBO)-controlled study ( NCT02955212 ) 1 . Methods Pts were randomized to 12 weeks of blinded treatment with UPA 15 mg once daily (QD) or PBO, in combination with csDMARDs. Primary and secondary endpoints were analyzed in a Chinese subgroup, including American College of Rheumatology criteria (ACR) responses, remission and low disease activity measures. Safety was analyzed for pts who received ≥1 dose of study drug. Results 228 Chinese pts (67.5% of overall trial population) were randomized and took at least one dose of study drug. Baseline characteristics were generally balanced between UPA and PBO. 46% and 35.1% used methotrexate (MTX) alone as concomitant csDMARD in UPA and PBO group, respectively. 38.9% in UPA and 43.0% in PBO group used concomitant csDMARDs other than MTX and 15.0% and 21.9% respectively used a combination. At week 12, more Chinese pts receiving UPA achieved the primary endpoint of ACR20 compared with PBO (71.9% vs 31.6%, nominal p&lt;0.001). UPA also showed greater improvements in all secondary endpoints vs PBO at Week 12 (Table 1), including ACR50 and ACR70, mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form 36-item Health Survey-Physical Component Summary (SF-36 PCS), as well as proportion of pts achieving low disease activity based on DAS28-CRP ≤3.2 and Clinical Disease Activity Index (CDAI) ≤10, and clinical remission based on DAS28-CRP &lt;2.6. Onset of response was rapid with more pts receiving UPA achieving ACR20 by Week 1 versus PBO (25.4% vs 5.3%, nominal p&lt;0.001). Through Week 12 treatment-emergent adverse events (TEAEs) occurred in 57.9% of pts on UPA and 49.1% on PBO. The rate of pts with serious AEs (SAEs) was numerically higher with UPA than with PBO (6.1% vs 4.4%). TEAEs reported in ≥ 3% of subjects and with a higher rate on UPA vs. PBO were: upper respiratory tract infection, alanine aminotransferase increased, aspartate aminotransferase increased, hypertension, diarrhea, and leukopenia. Overall safety was consistent with the trial population 1 and similar with the reported safety profile of the global clinical program 2 . Table 1. Summary of Efficacy Endpoint Results at Week 12 in Chinese Subgroup Endpoint a UPA 15mg (N=114) PBO (N=114) Primary endpoint ACR20, % 71.9*** 31.6 Secondary endpoints Δ DAS28-CRP -2.42*** -0.75 Δ HAQ-DI -0.55*** -0.11 Δ SF-36 PCS 7.63 b *** 2.94 c DAS28-CRP ≤3.2, % 46.5*** 9.6 DAS28-CRP &lt;2.6, % 28.1*** 1.8 CDAI ≤10, % 33.3*** 7.0 ACR50, % 39.5*** 7.0 ACR70, % 16.7*** 2.6 ACR20 at Week 1, % 25.4*** 5.3 ***Nominal p&lt;0.001 vs PBO a Non-responder imputation for binary endpoints; ANCOVA with multiple imputation for DAS28(CRP) and HAQ-DI; mixed model repeated measures for other continuous endpoints. Δ: mean change from baseline b N=106 c N=104 Conclusion UPA demonstrated clinical and functional improvement in Chinese csDMARD-IR RA pts. The safety of UPA was comparable with the overall study population and with the safety seen in the global Phase 3 program. References [1]Zeng X, Zhao D, Radominski SC, et al. Int J Rheum Dis. 2021;24:1530–1539. [2]Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Ann Rheum Dis 2021;80:304–311. Acknowledgements AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Disclosure of Interests Xiaofeng Zeng: None declared, Yi Liu: None declared, Jiankang Hu: None declared, Jingyang Li: None declared, Yongfu Wang: None declared, Dongbao Zhao: None declared, Lijun Wu: None declared, Zhengyu Xiao: None declared, ZHIJUN LI: None declared, Jian Xu: None declared, Sebastian Meerwein Shareholder of: may own AbbVie stock or options, Employee of: AbbVie employee, Yunxia Xie Shareholder of: may own AbbVie stock or options, Employee of: AbbVie employee, Peiwen Liang Employee of: AbbVie